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Biomedical subjects

K Kanazawa

Publications and source records attributed to K Kanazawa.

At least 217 records · Page 12Linked to original sources

[Promoting effect of endogenous TSH on carcinogenesis of rat thyroid transplanted into the spleen].

In an attempt to clarify a modifying effect of TSH on thyroid tumorigenesis, we carried out intrasplenic thyroid autotransplantation in rats treated with a thyroid carcinogen, diisopropanolnitrosamine (DIPN). Experiments comprised 3 groups of Wistar male rats: Group I (effective no., 15), total thyroidectomy plus hemithyroid transplantation 2 weeks after subcutaneous injection of DIPN at a dose of 2.4g/kg BW; group II (effective no., 22), DIPN alone; group III (effective no., 18), transplantation alone. The thyroid lesions of all rats at week 28 were examined by histopathology and enzyme histochemistry for gamma-glutamyl transpeptidase (GGT). Periodical radioimmunoassay for serum T3, T4 and TSH revealed low levels of T3 & T4 for at least 10 weeks and increased level of TSH until week 18 after the transplantation. Altered foci (AF) occurred in 36% and 6% of rats in group I and group II, respectively, whereas neoplastic nodules (NN) were found in 53% of rats only in group I. Both AF and NN displayed a positive reaction for GGT which was considered to be a useful marker for preneoplastic and neoplastic thyroid lesions. The present data are indicative that increased serum level of TSH for a significant period may exert a promoting effect on thyroid tumorigenesis.

Animals↗

[Isolation of cisplatin-resistant subline from human ovarian cancer cell line and analysis of its cell-biological characteristics].

The cisplatin (CDDP)-resistant subline TYK-nu (R) was developed by culturing TYK-nu (human ovarian cancer cell line in vitro) with exposure to CDDP in stepwise increasing concentrations. The characteristics of both cell lines were compared and the results were as follows; 1. Both cell lines formed a monolayer in a pavement-like arrangement and large cells were occasionally present in TYK-nu (R) rather than TYK-nu. The population doubling time of TYK-nu and TYK-nu (R) was 43 hr and 48 hr, respectively. 2. IC50 (microgram/ml) in 96 hr treatment with CDDP and carboplatin (CBDCA) was 0.035 and 0.5 in TYK-nu and 0.62 and 2.0 in TYK-nu (R), respectively. 3. In the intracellular CDDP concentration, there was no marked difference between TYK-nu and TYK-nu (R) after CDDP (2.0 micrograms/ml) treatment in 2hr. 4. After treatment with CDDP (0.2 microgram/ml) or CBDCA (2.0 micrograms/ml), a decrease in S and G2 + M compartments was observed in the pattern of the DNA histogram of TYK-nu, but not in that of TYK-nu (R). 5. The majority of chromosomes in both cell lines were in hyperdiploid areas and the mode of TYK-nu and TYK-nu (R) was 56 and 51, respectively. The karyotype of TYK-nu (R) showed deletion of chromosome 7q. Thus, compared to TYK-nu, TYK-nu (R) was 17.7 times more resistant to CDDP and 4 times more resistant to CBDCA. The results suggest that the mechanism of resistance to CDDP may be due to genetic changes at the cellular level.

Carboplatin↗

[Immunohistochemical analysis of the expression of HLA on the trophoblast of normal pregnancy].

The expression of MHC class II antigens (HLA-DR, -DP, -DQ) on trophoblast was analyzed by an immunoperoxidase technique using monoclonal antibodies. Tissues were obtained after pregnancy hysterectomy with the medical indications and after normal deliveries. They were snap-frozen in liquid nitrogen, cut in a cryostat and fixed in acetone for 10 minutes. Mouse monoclonal antibodies used in this study were anti-HLA-ABC (W6/32, Sera lab), anti-HLA-DR (Cappel), anti-HLA-DP (B7/21, Becton Dickinson) and anti-HLA-DQ (anti-Leu-10, Becton Dickinson) in addition to anti-cytokeratin (CAM5.2, Becton Dickinson) to recognize trophoblast. In the first trimester, HLA-DP could be identified on cytotrophoblastic cell column, cell island, extravillous trophoblast invading the decidua basalis, which were positive for HLA-ABC, and villous cytotrophoblast. In term placenta, villous syncytiotrophoblast and extra-villous trophoblast found in the decidua were positive for HLA-DP. In contrast, no trophoblast reacted with anti-HLA-DR or anti-HLA-DQ.

Antibodies, Monoclonal↗

[Immunohistochemical study on the MHC class I antigen expression on squamous cell carcinoma of the uterine cervix].

Immunohistological analysis was performed to detect MHC Class I antigen expression on uterine cervical squamous cell carcinomas of 23 patients using a monoclonal antibody (W6/32) to recognize a monomorphic determinant of HLA-ABC and an antibody (MA2.2) to react only with cells typed as HLA-A2. The results were as follows. 1. In 2 of 23 cases examined, cancer cells lacked reactivity with W6/32, although normal epithelial cells and connective stromal cells surrounding cancer nests were clearly positive for the antibody in all cases. 2. Of the remaining 21 cases, fourteen cases were judged to be HLA-A2 positive, based on the obvious staining of the stromal cells with MA2.2. Of these 14 only 5 carcinomas were positive for HLA-A2, and the cancer cells in the other 9 cases failed to bind MA2.2. These data suggest that in most clinically diagnosed patients, cancer cells do not have their own MHC Class I products on their cell surfaces phenotypically, and this unique property may be related to the biological characteristic that permits cancer cells to survive and proliferate unrestrictedly in vivo, mainly escaping from the immune-surveillance system under cytotoxic T lymphocytes (CTLs), which need to recognize not only cancer-specific (associated) antigen(s) but also the self-MHC Class I products to kill the cancer cells efficiently.

Adult↗

Weber-Christian disease associated with multiple perforations of the ileum and colon.

Panperitonitis developed in a 57-yr-old Japanese man during the course of Weber-Christian disease (WCD). Emergent operation disclosed three perforations of the ascending colon and two of the distal ileum. Histological study of the surgical specimen showed that all perforations were located at the centers of acute subserosal panniculitic foci. No vasculitis was discerned. In the previously reported three cases of WCD with intestinal perforation, perforation was solitary and seen in the small intestine. The cause of perforation was considered to be vasculitis in two cases. In the remaining one, panniculitis around the perforation was in chronic granulomatous stage. This was the first case of WCD in which acute subserosal panniculitis caused multiple ileocolonic perforations.

Acute Disease↗

Effect of orally administered 9-oxononanoic acid on lipogenesis in rat liver.

9-Oxononanoic acid, which is one of the major products of the autoxidation of linoleic acid, was administered orally to rats and its effect on hepatic lipid metabolism was investigated. The de novo synthesis of fatty acids was strongly reduced 30 h after the administration of 100 mg of 9-oxononanoic acid as compared to that in the saline-administered group. Activity of acetyl-CoA carboxylase decreased by 60% and the activity of carnitine palmitoyltransferase increased by 35% in the test group. The level of triacylglycerols in serum was low and the level of free fatty acids remained unchanged. Thus, the administration of 9-oxononanoic acid decreased hepatic lipogenesis. It is generally believed that the reduction in lipogenesis is facilitated by a decrease in the NADPH level. The ratio of NADPH/NADP in the test group, however, became high as compared to that in the control group, and the activities of glucose 6-phosphate and isocitrate dehydrogenases increased. On the other hand, the levels of CoA derivatives, especially long-chain acyl-CoA, were higher in the test group than in the control. Therefore, the reduction of hepatic lipogenesis in the 9-oxononanoic acid group could be attributed to the inhibition of acetyl-CoA carboxylase by the accumulated long-chain acyl-CoA.

Acetyl-CoA Carboxylase↗

Intraoperative irrigation and primary resection for obstructing lesions of the left colon.

The treatment of choice for left sided colonic obstruction is still controversial. We tried primary resection and anastomosis with the aid of intraoperative irrigation of the dilated proximal colon. Twenty-one cases of obstructive carcinoma of the left colon and four cases of sigmoid colon volvulus were managed using this approach. After the antegrade or retrograde intraoperative irrigation, primary resection and anastomosis without colostomy was performed in all 25 cases. There was only one case with anastomotic leakage. The satisfactory results of our present study and of the previous reports of intraoperative irrigation lead us to recommend intraoperative irrigation and primary anastomosis for left sided colonic obstruction except when the general condition of a patient is very poor or when the prognosis is expected to be poor due to the advanced spread of carcinoma.

Adult↗

Mutagen formed from tryptophan reacted with sodium nitrite in acidic solution.

The reaction products from L-tryptophan treated with nitrite under acidic conditions were investigated for mutagenic activity with the Salmonella typhimurium his reversion assay and for DNA-damaging activity using the rec-assay. The diethyl ether extract of the reaction mixture showed 8 spots on thin-layer chromatography (TLC). One compound from the TLC had high mutagenic activity for TA98 without S9 mix, with little DNA-damaging activity. The mutagen was purified and identified by instrumental analysis as 2-hydroxy-(1-N-nitrosoindole)propionic acid (NIHP). The mutagenic activity of NIHP was determined by the induced mutation frequency method; the induced mutation frequency was about 19.2 X 10(-5) at a dose level of 160 micrograms/plate.

Acids↗

Clinical evaluation of focal excision of myometrial lesion for treatment of invasive hydatidiform mole.

To determine the clinical significance of conservative surgical therapy, namely focal excision of myometrial molar deposits, 22 patients with invasive hydatidiform mole (HM) who had received the therapy were analysed for their postoperative clinical course and reproductive performance. They were operated on because of their prolonged HCG regression curve and the presence of abnormal shadows in the uterine wall revealed by pelvic angiography, ultrasonography and computerized tomography after evacuation of intra-uterine molar tissue. A definitive diagnosis of invasive HM was established histopathologically in all of the extirpated materials. Seven of the patients were given postsurgical chemotherapy because of prolongation of their HCG decrease after the operation. The following items were emphasized as necessary criteria when selecting patients for surgery consisting in complete resection of the myometrial lesion: (1) urinary HCG titers below 10,000 IU/day; (2) no evidence of pulmonary metastatic involvement; or (3) metastases in the lungs, controlled with chemotherapy prior to the operation. Their reproductive performance was almost the same as that of comparable patients who were treated by chemotherapy alone.

Adult↗

The effects of orally administered linoleic acid and its autoxidation products on intestinal mucosa in rat.

Linoleic acid and its autoxidation products, hydroperoxides and their secondary products, were orally administered to rats (350 mg each/rat). Hemorrhage was seen in the alimentary canal at 6 h after the dose of hydroperoxides. To examine their toxicities on intestinal mucosa, the activities of mucous enzymes (sucrase, maltase, and alkaline phosphatase) were measured. Hydroperoxides and their secondary products decreased the enzyme activities in jejunum at 6 h after the doses and increased them in both jejunum and ileum at 15 h, as compared to linoleic acid or saline solution. The decrease of enzyme activity was marked in the hydroperoxide group and the increase was marked in the secondary product group. Then, in in vitro experiments, the effects of autoxidation products on these enzymes were determined. Autoxidation products inactivated only alkaline phosphatase. Thus, the results in vivo disagreed with those in vitro. It was assumed that autoxidation products orally administered attacked a membrane of intestinal microvilli whereas in vitro they directly affected the enzymes.

Administration, Oral↗

[Morphological and immunohistochemical study on specimens of trophoblastic diseases in which the presence of a villous formation could not be established].

The histopathological discrimination between malignant trophoblastic diseases and benign trophoblastic diseases depends on the presence or absence of a villous structure. However, molar extravillous trophoblasts and cells in some placental site trophoblastic tumors (PSTT) of a benign nature, lack a villous structure. We therefore observed the morphology of trophoblastic cells which do not constitute a villous structure, including choriocarcinoma cells, and analyzed the location of placental proteins in these cells immunohistochemically. The results were as follows: 1. Molar extravillous trophoblasts were composed of large mononuclear cells and multinuclear cells. Most of them were positive for hPL and negative for hCG and SP1. 2. Choriocarcinoma consisted of cytotrophoblast-like cells, syncytiotrophoblast-like cells, large mononuclear cells and multinuclear cells resembling large mononuclear cells. HCG was noted in syncytiotrophoblast-like cells and large mononuclear cells, while hPL and SP1 were found only in syncytiotrophoblast-like cells. 3. PSTT was made up of large mononuclear cells and multinuclear cells which contained abundant hPL and very little hCG and SP1 or none at all. Molar extravillous trophoblasts were clearly distinguishable from choriocarcinoma cells in terms of their morphology and the location of placental proteins. In contrast, it seemed difficult to distinguish cells of PSTT from molar extravillous trophoblasts on a cell level.

Chorionic Gonadotropin↗

[Recently experienced ten cases of insulinoma--preoperative diagnosis of localization and intraoperative simultaneous monitoring of glucose and insulin].

We have experienced 10 cases of insulinoma during the last 10 years from 1977 to 1986. All cases had strong hypoglycemic symptoms such as disturbance of consciousness, and insulinoma still tended to be misdiagnosed as epilepsy. The diagnosis of insulinoma was easily available from serum IRI (immunoreactive insulin)/plasma glucose ratio in all of the ten cases. As preoperative procedures for the diagnosis of localization, arteriography, computed tomography and portal blood sampling were positive in 6 of 8, 4 of 6 and 2 of 2 patients, respectively. At operation, all insulinomas could be identified by digital palpation. We performed simple excision of the tumor in 6 patients and distal pancreatectomy in 4 patients. The tumors were solitary and benign in all patients, ranging in size from 1.0 cm to 4.5 cm. Three cases were presented as case reports. In these cases, portal blood sampling and/or intraoperative monitoring of plasma glucose and serum IRI were performed. Portal blood sampling was effective even for a case which was negative in image diagnostic procedures. Furthermore, simultaneous monitoring of plasma glucose and serum IRI by quick radioimmunoassay seemed to be a good guide to the completeness of resection of insulin producing tumors.

Adenoma, Islet Cell↗

[A case of multiple aneurysms originated from the superior mesenteric artery branch, and a review of literature].

A case of multiple aneurysm of superior mesenteric artery (SMA) branch is presented. A 54-year-old man with sudden onset of back pain was admitted to our hospital. Severe abdominal pain was developed and he fell into shock. Selective angiography of the SMA demonstrated aneurysm of the accessory middle colic artery to splenic flexure. Laparotomy disclosed much intraperitoneal blood and a large clot under the pancreatic body with a gushing hemorrhage. The bleeding vessel was ligated and sutured. The postoperative course was uneventful, but the subsequent angiography revealed another aneurysm of SMA branch, which was not able to be seen in the previous angiography because of overlapping with main SMA trunk. Resection of the aneurysm was done. The etiology of the latter aneurysm was suggested to be medial degeneration histologically. Fourty-nine cases of SMA aneurysm from the Japanese literature were reviewed and discussed. Emphasis is placed on early diagnostic laparotomy for appropriate management and the role of angiography in confirmation of bleeding site in case of spontaneous intraabdominal hemorrhage.

Aneurysm↗

[Antitumor effect of UFT on human ovarian cancer grafted to nude mice and 5-FU concentration in tumor and normal tissues].

Antitumor effects of UFT, tegafur (FT-207), cisplatin (CDDP) and the combination of UFT with CDDP on a human ovarian cancer xenograft in nude mice and the concentration of 5-FU in the tumor tissue and major organs were studied. UFT (48.6mg/kg/day X 20) or tegafur (15.0mg/kg/day X 20) was daily administrated orally, and CDDP (5mg/kg/day X 3) was administrated intraperitoneally at an 7-day interval. The inhibition rates of the tumor growths were 49.6% with UFT, -2.3% with tegafur and 17.7% with CDDP, respectively. In the combination of UFT with CDDP, severe side effect were observed. The concentration of 5-FU in UFT-treated group was higher than tegafur group: about 2 times in the tumor, 5 times in the liver, 9 times in the kidney and 4 times in the spleen, respectively. In the combination of UFT with CDDP, the concentration of 5-FU in major organs, especially in the kidney, in nude mice that died at 10 day after drug administration were higher than in those of UFT. These findings indicate that UFT increases the intratumoral concentration of 5-FU to elicit better antitumor effect and also the concentration of 5-FU in various normal organs after long time administration.

Animals↗

Effect of orally administered secondary autoxidation products of linoleic acid on carbohydrate metabolism in rat liver.

The effects of orally administered secondary autoxidation products of linoleic acid in rat liver were investigated. Their administration led to two toxic effects on hepatic carbohydrate metabolism, as compared to the administration of saline or linoleic acid used as controls. One effect was depletion of glucose 6-phosphate and fructose 6-phosphate caused by the reduction of glycolysis and glycogenolysis, accompanied by decreases in glycogen synthesis and pentose phosphate cyclic activity. The reduction in these metabolic systems seems unlikely to occur because phosphofructokinase was regulated by ATP or citrate enzymatically, because their accumulation in the liver was not detected in the secondary products. Another toxic effect was the depletion of oxaloacetate and isocitrate caused by the reduction in enzyme activity of the mitochondrial citrate cycle. On the basis of these results, the hepatotoxic effects of secondary products are discussed as follows: the incorporated secondary products impaired the activities of hexokinase and phosphoglucomutase in the liver. The reduction in these enzyme activities resulted in the depletion of glucose 6-phosphate and fructose 6-phosphate, which led ultimately to decreases in the activities of phosphofructokinase, the pentose phosphate cycle, and glycogen synthesis. Moreover, the secondary products disturbed the mitochondrial membrane, resulting in a decrease in the activity of the citrate cycle, which was accompanied by depletion of its metabolites.

Adenine Nucleotides↗